CN101247794B - 阿肽地尔的制剂 - Google Patents
阿肽地尔的制剂 Download PDFInfo
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- CN101247794B CN101247794B CN2006800072361A CN200680007236A CN101247794B CN 101247794 B CN101247794 B CN 101247794B CN 2006800072361 A CN2006800072361 A CN 2006800072361A CN 200680007236 A CN200680007236 A CN 200680007236A CN 101247794 B CN101247794 B CN 101247794B
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- pulmonary hypertension
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- 230000004097 bone metabolism Effects 0.000 description 1
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 150000007516 brønsted-lowry acids Chemical class 0.000 description 1
- 150000007528 brønsted-lowry bases Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000001354 calcination Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- LFHISGNCFUNFFM-UHFFFAOYSA-N chloropicrin Chemical compound [O-][N+](=O)C(Cl)(Cl)Cl LFHISGNCFUNFFM-UHFFFAOYSA-N 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000005308 flint glass Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 1
- 229940043257 glycylglycine Drugs 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
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- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
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- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
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- 229960003080 taurine Drugs 0.000 description 1
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- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000011123 type I (borosilicate glass) Substances 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
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Images
Abstract
Description
有效pH范围 | pKa 25℃ | 缓冲液 |
2.7-4.2 | 3.40 | 苹果酸盐(pK1) |
3.0-4.5 | 3.75 | 甲酸盐 |
3.0-6.2 | 4.76 | 柠檬酸盐(pK2) |
3.2-5.2 | 4.21 | 琥珀酸盐(pK1) |
3.6-5.6 | 4.76 | 醋酸盐 |
3.8-5.6 | 4.87 | 丙酸盐 |
4.0-6.0 | 5.13 | 苹果酸盐(pK2) |
4.9-5.9 | 5.23 | 吡啶 |
5.0-6.0 | 5.33 | 哌嗪(pK1) |
5.0-7.4 | 6.27 | 卡可酸盐 |
5.5-6.5 | 5.64 | 琥珀酸盐(pK2) |
5.5-6.7 | 6.10 | MES |
5.5-7.2 | 6.40 | 柠檬酸盐(pK3) |
5.5-7.2 | 6.24 | 马来酸盐(pK2) |
5.5-7.4 | 1.70,6.04,9.09 | 组氨酸 |
5.8-7.2 | 6.46 | bis-tris |
5.8-8.0 | 7.20 | 磷酸盐(pK2) |
6.0-12.0 | 9.50 | 乙醇胺 |
6.0-7.2 | 6.59 | ADA |
6.0-8.0 | 6.35 | 碳酸盐(pK1) |
6.1-7.5 | 6.78 | ACES |
6.1-7.5 | 6.76 | PIPES |
6.2-7.6 | 6.87 | MOPSO |
6.2-7.8 | 6.95 | 咪唑 |
6.3-9.5 | 6.80,9.00 | BIS-TRIS丙烷 |
6.4-7.8 | 7.09 | BES |
6.5-7.9 | 7.14 | MOPS |
6.8-8.2 | 7.48 | HEPES |
6.8-8.2 | 7.40 | TES |
6.9-8.3 | 7.60 | MOBS |
7.0-8.2 | 7.52 | DIPSO |
7.0-8.2 | 7.61 | TAPSO |
7.0-8.3 | 7.76 | 三乙醇胺(TEA) |
7.0-9.0 | 0.91,2.10,6.70,9.32 | 焦磷酸盐 |
7.1-8.5 | 7.85 | HEPPSO |
7.2-8.5 | 7.78 | POPSO |
阿肽地尔浓度 | 0.033 mg/mL | 0.066 mg/mL | 2mg/mL |
0.15M氯化 钠,2-8℃, 10个星期 | 化验百分比损 失 | -7.9 | -2.7 | -1.7 |
0.12M柠檬 酸盐缓冲液, pH 5.7,2-8 ℃,10个星 期 | 化验百分比损 失 | -6.5 | +1.15 | 没有测试 |
成分 | 重量% (w/v) |
阿肽地尔 | 0.0066-0.5 |
氯化钠 | 0.9 |
用于注射的水 | 100mL |
成分 | 重量% (w/v) |
阿肽地尔 | 0.0066-1.0 |
甘露醇 | 4.0 |
氯化钠 | 0.16 |
用于注射的水 | 100mL |
成分 | 重量% (w/v) |
阿肽地尔 | 0.001-1.0 |
柠檬酸盐缓冲液 (50mM,pH 5.8) | |
柠檬酸 | 0.227 |
柠檬酸三钠二水 合物 | 1.12 |
甘露醇 | 4.0 |
用于注射的水 | 100mL |
成分 | 重量% (w/v) |
阿肽地尔 | 0.001-1.0 |
柠檬酸盐缓冲液 (120mM,pH 5.7) | |
柠檬酸 | 0.59 |
柠檬酸三钠二水 合物 | 2.62 |
乙二胺四乙酸三 钠四水合物 | 0.23 |
用于注射的水 | 100mL |
成分 | 重量% (w/v) |
阿肽地尔 | 0.001-1.0 |
醋酸盐缓冲液 (30mM,pH 5.7) | |
醋酸盐钠三水合物 | 0.732 |
冰乙酸 | 0.0371 |
甘露醇 | 4.3 |
用于注射的水 | 100mL |
成分 | 重量%(w/v) |
阿肽地尔 | 0.001-1.0 |
磷酸盐缓冲液 (50mM,pH 6.0) | |
磷酸氢二钠 | 0.0422 |
磷酸二氢二钠单水合物 | 0.649 |
氯化钠 | 0.4 |
聚山梨酸酯80 | 0.02 |
用于注射的水 | 100mL |
成分 | 重量% (w/v) |
阿肽地尔 | 0.001-1.0 |
磷酸盐缓冲液 (20mM,pH 5.8) | |
磷酸氢二钠 | 0.023 |
磷酸二氢二钠单水合物 | 0.254 |
甘露醇 | 4.2 |
聚山梨酸酯80 | 0.02 |
用于注射的水 | 100mL |
成分 | 重量% (w/v) |
阿肽地尔 | 0.001-1.0 |
醋酸盐缓冲液 (12mM,pH 5.9) | |
醋酸盐钠三水合物 | 0.308 |
冰的乙酸 | 0.008 |
甘露醇 | 4.4 |
聚山梨酸酯80 | 0.02 |
间甲酚 | 0.225 |
用于注射的水 | 100mL |
成分 | 重量(%) |
阿肽地尔 | 0.0066-1.0 |
氯化钠 | 0.15% |
甘露醇 | 4.1 |
聚山梨酸酯80 | 0.02 |
间甲酚 | 0.3 |
用于注射的水 | 100mL |
成分 | 重量(%) |
阿肽地尔 | 0.001-1.0 |
甘露醇 | 5.0 |
用于注射的水 | 100mL |
Claims (19)
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DE102005010415 | 2005-03-07 | ||
US66282105P | 2005-03-18 | 2005-03-18 | |
US60/662,821 | 2005-03-18 | ||
PCT/EP2006/002084 WO2006094764A1 (en) | 2005-03-07 | 2006-03-07 | Formulation for aviptadil |
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CN108333360A (zh) * | 2017-01-19 | 2018-07-27 | 深圳市新产业生物医学工程股份有限公司 | 胃泌素释放肽前体稀释液及其应用和试剂盒 |
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Non-Patent Citations (4)
Title |
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C. Dufes 等."Brain delivery of vasoactive intestinal peptide (VIP)followingnasal administration to rats.International journal of Pharmaceutics255 1-2.2003,255(1-2),摘要、第89-90、94页. |
C. Dufes 等."Brain delivery of vasoactive intestinal peptide (VIP)followingnasal administration to rats.International journal of Pharmaceutics255 1-2.2003,255(1-2),摘要、第89-90、94页. * |
徐伟等.血管活性肠肽研究进展.药物生物技术9 6.2002,9(6),第367页. |
徐伟等.血管活性肠肽研究进展.药物生物技术9 6.2002,9(6),第367页. * |
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PT1855661E (pt) | 2011-07-05 |
DE602006021708D1 (de) | 2011-06-16 |
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